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Open AccessArticle

Delayed-Type Hypersensitivity Underlying Casein Allergy Is Suppressed by Extracellular Vesicles Carrying miRNA-150

1
Department of Immunology, Jagiellonian University Medical College, 31-121 Krakow, Poland
2
Section of Rheumatology, Allergy and Clinical Immunology, Yale University School of Medicine, New Haven, CT 06520, USA
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(4), 907; https://doi.org/10.3390/nu11040907
Received: 28 March 2019 / Revised: 12 April 2019 / Accepted: 18 April 2019 / Published: 23 April 2019
(This article belongs to the Special Issue Cow's Milk and Allergy)
In patients with non-IgE-mediated milk allergy, a cellular mechanism of delayed-type hypersensitivity (DTH) is considered. Recent findings prove that cell-mediated reactions can be antigen-specifically inhibited by extracellular vesicles (EVs) carrying miRNA-150. We sought to establish a new mouse model of DTH to casein and test the possibility of antigen-specific suppression of the inflammatory reaction. To produce soluble antigenic peptides, casein was subjected to alkaline hydrolysis. DTH reaction to casein was induced in CBA, C57BL/6, and BALB/c mice by intradermal (id) injection of the antigen. Cells collected from spleens and lymph nodes were positively or negatively selected and transferred to naive recipients intravenously (iv). CBA mice were tolerized by iv injection of mouse erythrocytes conjugated with casein antigen and following id immunization with the same antigen. Suppressive EVs were harvested from cell cultures and serum of tolerized donors by means of ultrafiltration and ultracentrifugation for further therapeutic utilization. The newly established mouse model of DTH to casein was mediated by CD4+ Th1 cells and macrophages, while EVs produced by casein-tolerized animals effectively suppressed effector cell response, in an miRNA-150-dependent manner. Altogether, our observations contribute to the current understanding of non-IgE-mediated allergy to casein and of the possibilities to downregulate this reaction. View Full-Text
Keywords: cow’s milk allergy; casein; cell-mediated reactions; delayed-type hypersensitivity; extracellular vesicles; miRNA-150 cow’s milk allergy; casein; cell-mediated reactions; delayed-type hypersensitivity; extracellular vesicles; miRNA-150
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Wąsik, M.; Nazimek, K.; Nowak, B.; Askenase, P.W.; Bryniarski, K. Delayed-Type Hypersensitivity Underlying Casein Allergy Is Suppressed by Extracellular Vesicles Carrying miRNA-150. Nutrients 2019, 11, 907.

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